Average Clinician-Measured Blood Pressures and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Ischemic Heart Disease in the EXAMINE Trial

William B White, Fatima Jalil, William C Cushman, George L Bakris, Richard Bergenstal, Simon R Heller, Yuyin Liu, Cyrus Mehta, Faiez Zannad, Christopher P Cannon, William B White, Fatima Jalil, William C Cushman, George L Bakris, Richard Bergenstal, Simon R Heller, Yuyin Liu, Cyrus Mehta, Faiez Zannad, Christopher P Cannon

Abstract

Background Blood pressure ( BP ) treatment goals in patients with diabetes mellitus and increased cardiovascular risk remain controversial. Our study objective was to determine cardiovascular outcomes according to achieved BP s over the average follow-up period in the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) trial. Methods and Results EXAMINE was a cardiovascular outcomes trial in 5380 patients with type 2 diabetes mellitus and recent acute coronary syndromes. Risks of major adverse cardiac events and cardiovascular death or heart failure were analyzed using a Cox proportional hazards model with adjustment for baseline covariates in 10-mm Hg increments of clinician-measured systolic BP from ≤100 to >160 mm Hg and diastolic BP from ≤60 to >100 mm Hg averaged during the 24 months after randomization. Based on 2015 guidelines from the American College of Cardiology, the American Heart Association and the American Society of Hypertension and 2017 American Diabetes Association guidelines, systolic BP s of 131 to 140 mm Hg and diastolic BP s of 81 to 90 mm Hg were the reference groups. A U-shaped relationship between cardiovascular outcomes and BP s was observed. Importantly, compared with the systolic BP reference group, adjusted hazard ratios for major adverse cardiac events and cardiovascular death or heart failure were significantly higher in patients with systolic BP s <130 mm Hg. Similarly, compared with the diastolic BP reference group, adjusted hazard ratios for major adverse cardiac events and for cardiovascular death or heart failure were significantly higher for diastolic BP s <80 mm Hg. Conclusions In patients with type 2 diabetes mellitus and recent acute coronary syndrome, average BP s <130/80 mm Hg were associated with worsened cardiovascular outcomes. These data suggest that intensive control of BP in patients with type 2 diabetes mellitus and ischemic heart disease should be evaluated in a prospective randomized trial. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00968708.

Trial registration: ClinicalTrials.gov NCT00968708.

Keywords: blood pressure; cardiovascular outcomes; diabetes mellitus.

Figures

Figure 1
Figure 1
Achieved and baseline blood pressures (BPs) and cardiovascular outcomes. Upper panels show baseline and achieved systolic BP (SBP) and major adverse cardiac events (MACE) and cardiovascular (CV) death or heart failure. Lower panels show baseline and achieved diastolic BP (DBP) and MACE or CV death and heart failure. Shaded areas represent the upper and lower 95% confidence limits for the hazard ratios (HRs).
Figure 2
Figure 2
Cubic spline curves depicting the relationship between average clinician blood pressure and the hazard ratio for the primary end point in EXAMINE (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke). Upper panel depicts systolic blood pressure; lower panel shows diastolic blood pressure. The lowest event rates occurred at systolic blood pressures of 132 to 136 mm Hg and at diastolic blood pressures of 77 to 80 mm Hg. CI indicates confidence interval; EXAMINE, Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care; HR, hazard ratio.

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